Hindawi

International Journal of Endocrinology

Volume 2018, Article ID 1528437, 6 pages
https://doi.org/10.1155/2018/1528437

Research Article
Fasting-Evoked En Route Hypoglycemia in Diabetes (FEEHD): An
Overlooked Form of Hypoglycemia in Clinical Practice

Saleh Aldasouqi ,1 Samia Mora,2 Gaurav Bhalla,1 Naveen Kakumanu,1 William Corser,3
George Abela,4 Mohammad Dlewati,5 Kathleen Estrada,6 Abdul Almounajed ,5
Tarek Tabbaa,7 Jamal Hammoud,8 and Cathy Newkirk9
1
Division of Endocrinology, Department of Medicine, College of Human Medicine, Michigan State University, USA
2
Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, USA
3
College of Osteopathic Medicine, Michigan State University, USA
4
Division of Cardiology, Department of Medicine, College of Human Medicine, Michigan State University, USA
5
University of Michigan-Flint, USA
6
College of Human Medicine, Michigan State University, USA
7
Wayne State University, USA
8
College of Human Medicine-Flint, Michigan State University, USA
9
Michigan State University Extension-Flint, USA

Correspondence should be addressed to Saleh Aldasouqi; saleh.aldasouqi@hc.msu.edu

Received 21 May 2018; Revised 7 August 2018; Accepted 26 August 2018; Published 24 October 2018

Academic Editor: Tatsuya Kin

Copyright © 2018 Saleh Aldasouqi et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. Many patients with diabetes opt to fast for lab tests, especially for lipid profiles, thus missing breakfast. In parallel,
recent studies and international guidelines have indicated that routine fasting for lipid panels may not be necessary. Missing
breakfast while fasting for lab tests may invoke hypoglycemia, if patients are not properly instructed about adjusting diabetes
medications on the night before or on the day of the lab test. Our group described this form of hypoglycemia and
introduced the term FEEHD to refer to it (fasting-evoked en route hypoglycemia in diabetes). In a recently published small
study, we reported a rate of occurrence of FEEHD of 27.1%. The objective of this study was to evaluate the rate of
occurrence of FEEHD in another clinic. Methods. Patients with diabetes were asked to complete a simple, 2-page survey
inquiring about hypoglycemic events while fasting for labs in the preceding 12 months. Results. A total of 525 patients
completed the surveys out of 572 patients invited (91.8% response rate). A total of 363 patients with complete data were
analyzed, with a mean age of 60.6 (SD 12.5) years. A total of 62 (17.1%) patients reported having experienced one or more
FEEHD events in the prior 12 months. Of the 269 patients who were at higher risk of FEEHD (on insulin secretagogues or
on insulin), 59 (21.9%) reported having experienced FEEHD. Only 33 of FEEHD patients (53%) recalled having contacted
their provider regarding the events and only 22 (35%) indicated having received some sort of FEEHD prevention
instructions. Conclusion. Our study shows a significant rate of occurrence of FEEHD in the real world (a clinical practice).
FEEHD is especially dangerous, as patients often commute (drive) to and from the laboratory facility (potential risk of traffic
accidents). Given study limitations, further studies are needed to assess prevalence of FEEHD in other settings and in the
general populations.

1. Introduction Therefore, hypoglycemia is practically the rate limiting step

in aggressive control of diabetes [1]. Hypoglycemic events
Hypoglycemia in patients with diabetes, defined as blood glu- are unpleasant and are associated with negative emotional,
cose below 70 mg/dl [1], is one of the most common adverse social, and behavioral consequences for patients and in
events in patients taking insulin or oral hypoglycemic agents. extreme cases leading to life-threatening arrhythmias and
2 International Journal of Endocrinology
sudden cardiac death [2, 3]. Fear of hypoglycemia is also an
important contributor to worse quality of life for patients with
diabetes, as such episodes can lead to patient dissatisfaction
with management and also affect physicians’ aggressiveness
in optimal management of diabetes leading to underutiliza-
tion of treatment regimens and failure to achieve optimal
glycemic targets [4, 5].
A conceivably overlooked cause of hypoglycemia is the
procurement of fasting labs, of which the lipid panel is the
most commonly ordered fasting lab test. Traditionally,
guidelines have recommended routine fasting lipid panels
[6, 7]. Recently, though, the notion of routine fasting lipid
panel in every patient has been challenged, with recent
European and Canadian guidelines endorsing nonfasting
lipid testing for routine clinical care and management
decisions [8–11].
By ordering fasting labs, we may not only be
inconveniencing patients, but we may also be inadvertently
putting them at risk for hypoglycemia [12–14]. A case report
from Thailand [15] reported on a patient who had hypogly-
cemia in the waiting room of a laboratory, while waiting for
a fasting lab. The patient had a sudden cardiac arrest that
led to the death of the patient (blood glucose during resusci-
tation was later reported to be 0 mg/dl). The patient was on a
sulphonylurea for her diabetes [15].
The acronym FEEHD was proposed to refer to this form
of hypoglycemia, and the acronym stands for “fasting-evoked
en route hypoglycemia in diabetes” [11, 13, 14, 16, 17].
FEEHD is arbitrarily defined by the following criteria: a
hypoglycemic event (blood glucose below 70 mg/dl) in
patients with diabetes who take insulin or sulfonylurea, or
both, who fast overnight for lab tests, and who commute
to the laboratory facility while fasting. Most of these hypo-
glycemia episodes go unreported and the patients are rarely
given instructions to change or adjust their medications
prior to fasting.
A recent pilot nonrandomized study [16] demonstrated a
significant occurrence of FEEHD episodes in clinical prac-
tice: 27.1% of 168 enrolled patients reported having experi-
enced one or more FEEHD events. This prompted the
current larger study, with the objective of estimating the rate
of occurrence of FEEHD in a different clinical setting (a dif-
ferent clinical practice), aiming at recruiting a higher number
of patients.
2. Methods
This was a nonrandomized, prospective survey (question-
naire) study. Study participants were patients who were
attending the study clinics for initial or follow-up visits. They
were enrolled in person by study coinvestigators (undergrad-
uate or medical students). Patient enrollment occurred per
the convenience and availability of study coinvestigators
(students) to attend clinics, to enroll study patients.
2.1. Participants. Adults with diabetes were recruited for this
study, which was conducted through a survey instrument at
two study sites: two locations of an endocrinology practice.
The research protocol was approved by the Institutional
Review Board, and all participants gave written informed
consent. This study was based on a recently published study,
utilizing similar inclusion and exclusion criteria [16]. Briefly,
inclusion criteria included adult patients who were able to
understand and answer the survey questions, who had a
confirmed diabetes diagnosis, and who were taking insulin
and/or oral hypoglycemic agents or noninsulin injectable
medications. Exclusion criteria included patients who were
unable to understand or complete the survey questionnaire
even with assistance, patients who were not taking medica-
tions regularly, and surveys that were not completely filled.
The study was conducted from March 1 to September
30, 2016, during outpatient clinic appointments at the
research sites.
2.2. Study Procedures: The Survey Questionnaire. The survey
was a simple language 2-page document asking about the
duration and type of diabetes, medication use, and any epi-
sodes of FEEHD in the preceding 12 months and if any
instructions were given to the patient about medication dose
adjustment prior to having laboratory tests. The survey was
adapted from the questionnaire used in a recent study [16].
At the end of the survey, a template notification was made
to instruct patients to notify their care providers of any hypo-
glycemic events to implement preventive measures.
2.3. Statistical Analysis. A series of descriptive statistical
analyses were completed to examine for missing data
patterns and distribution patterns of key study variables.
We then conservatively categorized continuous patient
characteristic data (e.g., age in years and years of diabetes
duration) into equivalent-sized tertile groups. To inform
the configuration of subsequent stepwise logistic regression
modeling procedures, a series of Pearson product-moment
bivariate correlation procedures were completed to examine
for suitable discrete model terms entered into subsequent
predictive models.
A basic two-tailed stepwise binary logistic regression pre-
dictive modeling procedure was then completed to examine
for statistically significant influences of whether fasting lab
patients experienced one or more FEEHD episode during
the 12-month reporting period. In such a procedure, each
model term is introduced one at a time, with model terms
showing significance levels of greater than 0.10 removed
from the final predictive model. A p value level of 0.05 was
observed to indicate statistical significance. All analyses were
completed using the S.P.S.S. version 24 analytic software.
3. Results
A total of 572 patients were invited to take part in the survey
(Table 1). A total of 525 patients agreed to complete the sur-
veys. A total of 47 patients either declined or were unable to
complete the surveys (response rate, 91.8%). The study coin-
vestigators listed the causes behind the declination or inabil-
ity of the 47 patients to complete the survey. These causes
were understandable, such as patient citing: “being in a
hurry”; “not interested in the study”; or “unable to complete
survey”, or the students would not enroll patients due to an
International Journal of Endocrinology 3

Table 1: Characteristics of patients and a summary of survey contacted their provider regarding the events. Only 22 of
responses. these 62 patients (35%) indicated having received some sort
of FEEHD prevention instructions, following notification
Total number of patients invited of provider.
572
to enroll in the study, N
Regarding their medication regimens, the number of
Total number of patients who completed patients on hypoglycemia-inducing oral hypoglycemic
525 (91.8%)
survey, N (survey response rate) agents (OHAs), namely, sulfonylureas and meglitinide ana-
Final analytic sample, excluding logues, insulin, or both, was 36, 215, and 18, respectively.
patients with no fasting labs (127) 363 Thus, the total at-risk population was 269 out of 363 patients
and patients with incomplete data (35) (74.1%). Of the “At-risk” patients, 59 out of 269 patients
Mean age (SD), years 60.6 (12.5) (21.9%) had one or more episodes of FEEHD during the pre-
Mean diabetes duration (SD), years 16.0 (11.5) ceding 12 months. A total of 35 out of these 59 patients (59%)
Sex, female 194 (53.2%) could recall their specific blood glucose readings at the time.
Patients reporting type 2 diabetes Their blood glucose readings averaged 56 mg/dl (SD 10),
298 (81.6%) with a range from 32 to 65 mg/dl.
mellitus, N (%)
Patients on hypoglycemia-inducing Of the total 363 patients analyzed, 149 patients (41%)
36 reported hypoglycemic events related to any cause (including
OHAs∗ (without insulin)
Patients on insulin without
those reporting FEEHD events) in the preceding 12 months.
hypoglycemia-inducing OHAs
215 These 149 patients who reported “all-cause” hypoglycemic
events could specifically recall at least one specific circum-
Patients on both insulin and
18 stance related to their hypoglycemia episode(s). These
hypoglycemia-inducing OHAs
included (frequently overlapping) reasons such as (a) fast-
Total at-risk patients for FEEHD∗∗ 269 (74.1%)
ing/eating less during prior night (n = 75), (b) exercising
∗∗∗
Total patients with FEEHD 62 (17.1%) (n = 55), (c) recent medication changes (n = 17), and (d)
Patients with FEEHD from “at-risk” multiple cited reasons (n = 29).
59 (21.9%)∗∗∗∗
patient group (prevalence) Upon further statistical analysis of the data, major non-
Multiple FEEHD episode patients 7 significant correlations with the occurrence of one or more
Patients educated by health care FEEHD episode(s) included (a) gender (p = 0 752), (b) age
131 (35.9%) category (p = 0 909), and (c) type of diabetes (p = 0 863).
prior to fasting labs
FEEHD = fasting-evoked en route hypoglycemia in diabetes; SD = standard
However, patient characteristics that were significantly
deviation; OHA = oral hypoglycemic agent. ∗ Sulfonylureas and meglitinide correlated with one or more FEEHD episode(s) included
analogues. ∗∗ At-risk patients: patients who had fasting labs done and were the following:
on insulin or hypoglycemia-inducing OHAs or both. ∗∗∗ FEEHD: fasting-
evoked en route hypoglycemia in diabetes. ∗∗∗∗ 3 patients who had (1) Hypoglycemic symptoms (p < 0 001)
FEEHD were not on any hypoglycemia-inducing OHA or insulin. They
were on metformin, saxagliptin, liraglutide, or canagliflozin. (2) Frequency of (all-cause) hypoglycemic episodes dur-
ing past year (p < 0 001)
ongoing acute illness during the visit such as having a (3) Taking insulin (p = 0 014)
hypoglycemic event.
After the exclusion of 127 (24.2%) patients who reported (4) Being on an insulin pump (p < 0 001)
no fasting labs during the 12 presurvey months and the
exclusion of 35 (7%) study participants with missing data, a 4. Discussion
final analytic sample of 363 respondents (169 men and 194
women) was examined. The detailed statistical analysis was These results indicate a high prevalence of FEEHD events
performed on the total number of these patients (i.e., 363 (17.1%) in clinical practice, which is relatively consistent with
respondents). The mean age of the analytic sample was 60.6 the 27.1% prevalence rate reported in a recently published
years (SD 12.5), and the duration of their diabetes averaged study [16]. The prevalence in the current study is 21.9% in
16.0 years (SD 11.5). A total of 298 (81.6%) patients reported at-risk patients (e.g., those on hypoglycemia-causing medica-
a diagnosis of type 2 diabetes mellitus. Of the total 363 tions such as insulin and/or sulfonylureas). With recent stud-
patients included in the analysis, 131 (36%) reported that ies [18] indicating increasing use of insulins, it is conceivable
they were previously educated about how to fast for labs that FEEHD may lead to increasing rates of hypoglycemia.
and how to take preventive measures such as medication The first study reporting on the occurrence of FEEHD in
adjustment (e.g., “reduce your insulin dose,” “have someone clinical practice was published as a pilot study in 2011 [12].
drive you to get your lab drawn”). The trigger for that study was the clinic’s nurses becoming
A total of 62 out of 363 patients (17.1%) reported having concerned about the repeated calls from the laboratory about
experienced at least one FEEHD event in the preceding 12 low glucose results (sometimes critically low). Those lab
months. Of these 62 patients who reported FEEHD events, results would be available to the lab staff hours after the blood
7 patients (11%) reported multiple FEEHD events. Only 33 draw earlier in the morning. This study was followed by two
of all the 62 FEEHD patients (53%) recalled having studies and a case series [13, 16, 17], in which the occurrence
4 International Journal of Endocrinology
of FEEHD was observed, confirming findings of the first
pilot study.
However, the aforementioned studies were limited by
sample size and lack of generalizability. In the first study
[12], the investigators retrospectively tracked hypoglycemic
events from their hospital’s laboratory records over a
preceding 21-month period. The same investigators then
implemented a hypoglycemia prevention program and then
undertook a follow-up study [13], following the same proto-
col of the first study tracking laboratory results in the subse-
quent 21 months. The investigators observed significant
prevention of hypoglycemia (FEEHD). In the 3rd publication
(a case series study), 4 cases of FEEHD [17] were captured
and were meticulously analyzed, for the purpose of better
understanding of the circumstances and causes of the hypo-
glycemic events. As such, the preceding 3 studies/case series
could not address the prevalence of FEEHD. The first study
to address prevalence [16] was a small-sized pilot study
(n = 168), which showed a significant prevalence of FEEHD
(27.1%) in a different clinical setting.
Collectively, these studies/case series [12, 13, 16, 17]
could not attract significant attention by the mainstream
medical communities or health organizations. Therefore,
we believe that the results of the current study are more con-
vincing, given the larger sample size. We hope that we have
been able to make a stronger case about the actual occurrence
of FEEHD, and we believe that it is an overlooked problem.
Of concern, our study showed that only 53% of patients
reported the FEEHD events to their providers, and only
35% received education regarding prevention of future
events, a finding that is consistent with the literature. It has
been reported that hypoglycemic events occurring outside
of clinics (at home or elsewhere), in general, are often not
reported by patients to their health care providers [19, 20].
The rate of occurrence of FEEHD as estimated by our
study in the total cohort is lower (17%) than that in the study
which was recently published [16] which was (27.1%),
though it is still significantly high in the “at-risk” population
(21.9%; patients on hypoglycemia-causing medications such
insulin and/or sulfonylureas who had fasting labs). This
lower rate percentage may be related to different sample
sizes, different practice methods, or different patient health
education (self-education or education by clinicians).
Of note, our study showed that only 36% of patients
received proper instructions about preparing for fasting for
labs. We have not found literature addressing if patients with
diabetes are educated or informed when fasting labs are
ordered, except for sporadic reports [21–23]. A small study
by Kackov and associates has found that the majority of out-
patients are not well informed about how to fast for lab tests
[21]. Only 15% and 19% of patients reported that they were
properly informed by a doctor or a nurse, respectively, about
preparation for fasting for labs. Furthermore, few other
investigators addressed inpatient fasting orders (for various
indications) and raised concerns about the appropriateness
of these orders [22], as well as the potential risk of hypoglyce-
mia in patients with diabetes [23].
A final note is that hypoglycemia has been linked to
increased risk of traffic accidents. As reported by Moghissi,
19% of patients with type 2 diabetes reported that hypoglyce-
mic events often occur during driving [19]. The American
Diabetes Association’s guidelines [24] state that “Clinically
significant hypoglycemia can cause acute harm to the person
with diabetes or others, especially if it causes falls, motor
vehicle accidents, or other injury.” Given these notions, there
is a conceivable risk of traffic accidents due to hypoglycemia
of the FEEHD type, if the hypoglycemia is severe. Hence, the
utilization of the word “en route” in the acronym, FEEHD,
emphasizes the observation that patients drive to and from
laboratory facilities [11, 13, 14, 16, 17]. Undoubtedly, it is a
routine that patients usually drive themselves to and from
lab facilities in the morning for fasting lab tests, typically on
the way to work.
In parallel to this ongoing research about the risk of fast-
ing for labs in patients with diabetes (FEEHD), there has
been a growing thrust of research questioning the necessity
of fasting when ordering lipid profiles, which are the most
commonly ordered fasting labs in clinical practice. Emerging
deliberations have been raised about the utility of fasting lipid
levels with various guidelines in Europe and Canada siding
with nonrequirement of fasting lipid panels [8–10, 25, 26].
In the United States, the tradition for fasting labs is deeply
entrenched in the psyche of patients and physicians alike.
In our clinical practice, it has been noticed that as soon as a
patient is informed that labs may be required, one of their
first responses is “but, I am not fasting today.”
This deeply rooted belief is not without reason as most
US guidelines continue to recommend fasting lipid panels;
though on a small scale, some US experts have recently
advocated nonfasting lipid panels [25, 26]. These emerging
opinions [26] have recently been expressed in few published
guidelines by US health organizations (namely, the US
Department of Veterans Affairs, the American Heart
Association, and the American Association of Clinical
Endocrinologists). However, these recommendations have
been worded at variable degrees of liberalization of lipid in
the nonfasting state, with the US Department of Veterans
Affairs being the most powerful recommendation [26].
4.1. Study Limitations. Our study has multiple limitations
that would limit the findings and conclusions of the study.
Furthermore, these limitations, as well, would prevent gener-
alization of the findings to other populations. The first and
foremost limitation of our study is that it was nonrando-
mized, and thus, the study findings will not comprise an
accurate prevalence estimation. Therefore, this study is con-
sidered a prevalence study, but rather a study which observed
the occurrence of FEEHD in a clinical setting. Secondly, our
study was based on a survey dependent upon patients’ recol-
lection of hypoglycemic episodes. This may have led to an
underestimation of prevalence, as patients with hypoglyce-
mia unawareness may never have realized that their glucose
is low. Another limitation is that we could not verify the exact
reason for patients getting fasting tests. We rather have based
our conclusions on our observation in our patients that lipid
panels are the most commonly ordered fasting labs.
Given the aforementioned limitations, we acknowledge
that this study could not be taken as an accurate estimate of
International Journal of Endocrinology
the prevalence of FEEHD in the general population. It rather
suggests that FEEHD is conceivably overlooked in clinical
practice, and this second study by our group confirms the
findings we reported in the previous, pilot study [16]. There-
fore, we propose that larger, population-based studies be
designed to evaluate the actual prevalence of FEEHD in the
general population. Our group is working on such a project.
5. Conclusion
Despite the aforementioned limitations, our study does prove
that there is a high rate of occurrence of iatrogenic fasting
hypoglycemia resulting from laboratory tests in patients on
medications which can induce hypoglycemia (FEEHD).
Our study has confirmed findings of prior studies that
FEEHD occurs in clinical practice and at an alarming preva-
lence rate. Ordering fasting lipid profiles will not only put
patients with diabetes at risk of hypoglycemia, but with the
changing guidelines in lipid testing, fasting for lipid tests
may not be necessary after all. It is imperative that health orga-
nizations, especially diabetes organizations, become more
aware of this issue and include specific educational guidelines
to prevent FEEHD. As the utility of fasting lipid panel has
been deemed doubtful and does not appear to be inferior to
nonfasting measurements, it may now be high time to amend
lipid management guidelines.
Abbreviations
FEEHD: Fasting-evoked en route hypoglycemia in diabetes.
Data Availability
The data used to support the findings of this study are
available from the corresponding author upon request.
Disclosure
The study was presented in part (as interim analysis) at
the 2017 annual meeting of the American Association of
Clinical Endocrinologists (AACE) in Austin, TX. The
abstract was selected by Healio.com’s Endocrine Today
magazine, for a video interview that was posted online fol-
lowing the meeting, in the following link: https://www.
healio.com/endocrinology/diabetes/news/online/%7B64d50
f7c-70a2-4726-b01e-4df4147dbbe0%7D/video-researchers-
call-to-end-fasting-requirement-in-blood-testing.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
Dr. Saleh Aldasouqi reports that he is a speaker for Janssen
Pharmaceutical and Alere Inc. Dr. Samia Mora reports that
she has received research support from Atherotech Diagnos-
tics and NHLBI. She also served as a consultant to Amgen,
Quest Diagnostics, Lilly, Pfizer, and Cerenis Therapeutics.
Dr. George Abela reports that he is a speaker for Merck,
Amgen, and Daiichi Sankyo. He also served as a consultant
to Kowa Pharmaceutical. He was a participant at Merck’s
US Thrombosis Advisory Board and Atherosclerosis Global
5
Therapeutic Experts Forum and he has received grant sup-
port. Dr. Naveen Kakumanu reports that he has received
research support from Novo Nordisk. Dr. Jamal Hammoud
reports that he is a speaker for Novo Nordisk, Sanofi, Merck,
Janssen, AstraZeneca, and Medtronic.
Acknowledgments
The authors would like to thank Ms. Jinie Shirey (Depart-
ment of Medicine, MSU College of Human Medicine, East
Lansing, MI) for assistance with manuscript preparation
and senior librarians Laura Smith, Michael Simmons, and
Steve Kalis (Sparrow Hospital, Lansing, MI) for assistance
with literature search. The authors also would like to thank
the clinical and support staff at both clinical sites for facilita-
tion of the study conduction and finally to thank all patients
who participated in the study.
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